A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

Mina A. Jhun; Michael Mendelson; Rory Wilson; Rahul Gondalia; Roby Joehanes; Elias Salfati; Xiaoping Zhao; Kim Valeska Emilie Braun; Anh Nguyet Do; Åsa K. Hedman; Tao Zhang; Elena Carnero-Montoro; Jincheng Shen; Traci M. Bartz; Jennifer A. Brody; May E. Montasser; Jeff R. O’Connell; Chen Yao; Rui Xia; Eric Boerwinkle; Megan Grove; Weihua Guan; Pfeiffer Liliane; Paula Singmann; Martina Müller-Nurasyid; Thomas Meitinger; Christian Gieger; Annette Peters; Wei Zhao; Erin B. Ware; Jennifer A. Smith; Klodian Dhana; Joyce van Meurs; Andre Uitterlinden; Mohammad Arfan Ikram; Mohsen Ghanbari; Deugi Zhi; Stefan Gustafsson; Lars Lind; Shengxu Li; Dianjianyi Sun; Tim D. Spector; Yii der Ida Chen; Coleen Damcott; Alan R. Shuldiner; Devin M. Absher; Steve Horvath; Philip S. Tsao; Sharon Kardia; Bruce M. Psaty; Nona Sotoodehnia; Jordana T. Bell; Erik Ingelsson; Wei Chen; Abbas Dehghan; Donna K. Arnett; Melanie Waldenberger; Lifang Hou; Eric A. Whitsel; Andrea Baccarelli; Daniel Levy; Myriam Fornage; Marguerite R. Irvin; Themistocles L. Assimes

doi:10.1038/s41467-021-23899-y

A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

Mina A. Jhun^*, Michael Mendelson, Rory Wilson, Rahul Gondalia, Roby Joehanes, Elias Salfati, Xiaoping Zhao, Kim Valeska Emilie Braun, Anh Nguyet Do, Åsa K. Hedman, Tao Zhang, Elena Carnero-Montoro, Jincheng Shen, Traci M. Bartz, Jennifer A. Brody, May E. Montasser, Jeff R. O’Connell, Chen Yao, Rui Xia, Eric BoerwinkleMegan Grove, Weihua Guan, Pfeiffer Liliane, Paula Singmann, Martina Müller-Nurasyid, Thomas Meitinger, Christian Gieger, Annette Peters, Wei Zhao, Erin B. Ware, Jennifer A. Smith, Klodian Dhana, Joyce van Meurs, Andre Uitterlinden, Mohammad Arfan Ikram, Mohsen Ghanbari, Deugi Zhi, Stefan Gustafsson, Lars Lind, Shengxu Li, Dianjianyi Sun, Tim D. Spector, Yii der Ida Chen, Coleen Damcott, Alan R. Shuldiner, Devin M. Absher, Steve Horvath, Philip S. Tsao, Sharon Kardia, Bruce M. Psaty, Nona Sotoodehnia, Jordana T. Bell, Erik Ingelsson, Wei Chen, Abbas Dehghan, Donna K. Arnett, Melanie Waldenberger, Lifang Hou, Eric A. Whitsel, Andrea Baccarelli, Daniel Levy, Myriam Fornage, Marguerite R. Irvin, Themistocles L. Assimes

^*Corresponding author for this work

Twin Research & Genetic Epidemiology

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.

Original language	English
Article number	3987
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23899-y
Publication status	Published - Dec 2021

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10.1038/s41467-021-23899-y

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Jhun, M. A., Mendelson, M., Wilson, R., Gondalia, R., Joehanes, R., Salfati, E., Zhao, X., Braun, K. V. E., Do, A. N., Hedman, Å. K., Zhang, T., Carnero-Montoro, E., Shen, J., Bartz, T. M., Brody, J. A., Montasser, M. E., O’Connell, J. R., Yao, C., Xia, R., ... Assimes, T. L. (2021). A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids. Nature Communications, 12(1), Article 3987. https://doi.org/10.1038/s41467-021-23899-y

@article{b482ab912f1f402ea1d87c597fede466,

title = "A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids",

abstract = "Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.",

author = "Jhun, {Mina A.} and Michael Mendelson and Rory Wilson and Rahul Gondalia and Roby Joehanes and Elias Salfati and Xiaoping Zhao and Braun, {Kim Valeska Emilie} and Do, {Anh Nguyet} and Hedman, {{\AA}sa K.} and Tao Zhang and Elena Carnero-Montoro and Jincheng Shen and Bartz, {Traci M.} and Brody, {Jennifer A.} and Montasser, {May E.} and O{\textquoteright}Connell, {Jeff R.} and Chen Yao and Rui Xia and Eric Boerwinkle and Megan Grove and Weihua Guan and Pfeiffer Liliane and Paula Singmann and Martina M{\"u}ller-Nurasyid and Thomas Meitinger and Christian Gieger and Annette Peters and Wei Zhao and Ware, {Erin B.} and Smith, {Jennifer A.} and Klodian Dhana and {van Meurs}, Joyce and Andre Uitterlinden and Ikram, {Mohammad Arfan} and Mohsen Ghanbari and Deugi Zhi and Stefan Gustafsson and Lars Lind and Shengxu Li and Dianjianyi Sun and Spector, {Tim D.} and Chen, {Yii der Ida} and Coleen Damcott and Shuldiner, {Alan R.} and Absher, {Devin M.} and Steve Horvath and Tsao, {Philip S.} and Sharon Kardia and Psaty, {Bruce M.} and Nona Sotoodehnia and Bell, {Jordana T.} and Erik Ingelsson and Wei Chen and Abbas Dehghan and Arnett, {Donna K.} and Melanie Waldenberger and Lifang Hou and Whitsel, {Eric A.} and Andrea Baccarelli and Daniel Levy and Myriam Fornage and Irvin, {Marguerite R.} and Assimes, {Themistocles L.}",

note = "Funding Information: We thank our Amish community and research volunteers for their long-standing partnership in research, and acknowledge the dedication of our Amish liaisons, field workers and the Amish Research Clinic staff, without which these studies would not have been possible. We thank the staff and participants of the ARIC study for their important contributions. We would also like to thank the families that participated in the GENOA study. The authors are grateful to the Rotterdam Study participants, the staff involved with the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of the Illumina 450 K methylation array data (EWAS data) for the Rotterdam Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We thank Mr. Michael Verbiest, Ms. Mila Jhamai, Ms. Sarah Higgins, Mr. Marijn Verkerk, and Lisette Stolk PhD for their help in creating the methylation database. We thank Ms. Mila Jhamai, Ms. Sarah Higgins, Marjolein Peters, MSc, Mr. Marijn Verkerk and Jeroen van Rooij, MSc for their help in creating the RNA array expression database. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant R01HL105756. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I). Funding was also supported by 5RC2HL102419 and R01NS087541. The CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 75N92021D00006; and NHLBI grants U01HL080295, R01HL087652, R01HL092111, R01HL105756, R01HL103612, R01HL111089, R01HL116747, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA) as well as Laughlin Family, Alpha Phi Foundation, and Locke Charitable Foundation. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Framingham Heart Study is funded by National Institutes of Health contract N01-HC-25195. The laboratory work for this investigation was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health and an NIH Director{\textquoteright}s Challenge Award (D. Levy, Principal Investigator). The GOLDN epigenetics study is funded by the NIH National Heart, Lung, and Blood Institute grant R01 HL104135-01. Support for the Genetic Epidemiology Network of Arteriopathy (GENOA) was provided by the National Heart, Lung and Blood Institute (HL054457, HL100185, HL119443, and HL133221) of the National Institutes of Health. German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universit{\"a}t, as part of LMUinnovativ. This work was supported by a grant (WA 4081/1-1) from the German Research Foundation. The TwinsUK epigenetic study received support from the ESRC (ES/N000404/1). The TwinsUK study funded by the Wellcome Trust; European Community{\textquoteright}s Seventh Framework Programme (FP7/2007–2013); National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. The PIVUS study was supported by Swedish Research Council (Grant no. 2012-1397), Knut och Alice Wallenberg Foundation (Grant no. 2013.0126), Swedish Heart-Lung Foundation (grant no. 20140422), and Swedish Diabetes Foundation (Grant no. 2013-024). The Rotterdam Study EWAS data was funded by the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by the Netherlands Organization for Scientific Research (NWO; project number 184021007) and made available as a Rainbow Project (RP3; BIOS) of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL). The generation and management of RNA-expression array data for the Rotterdam Study was executed and funded by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. The Women{\textquoteright}s Health Initiative data, WHI-BA23 and WHI-EMPC, were generated through an NHLBI Broad Agency Announcement contract (HHSN268201300006C) and a National Institute of Environmental Health Sciences grant (R01-ES020836). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Funding Information: Alan R Shuldiner is an employee of Regeneron Pharmaceuticals, Inc. Bruce M Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Kim Valeska Emilie Braun works in ErasmusAGE, a center for aging research across the life course funded by Nestl{\'e} Nutrition (Nestec Ltd.), Metagenics Inc. and AXA. Publisher Copyright: {\textcopyright} 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = dec,

doi = "10.1038/s41467-021-23899-y",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Jhun, MA, Mendelson, M, Wilson, R, Gondalia, R, Joehanes, R, Salfati, E, Zhao, X, Braun, KVE, Do, AN, Hedman, ÅK, Zhang, T, Carnero-Montoro, E, Shen, J, Bartz, TM, Brody, JA, Montasser, ME, O’Connell, JR, Yao, C, Xia, R, Boerwinkle, E, Grove, M, Guan, W, Liliane, P, Singmann, P, Müller-Nurasyid, M, Meitinger, T, Gieger, C, Peters, A, Zhao, W, Ware, EB, Smith, JA, Dhana, K, van Meurs, J, Uitterlinden, A, Ikram, MA, Ghanbari, M, Zhi, D, Gustafsson, S, Lind, L, Li, S, Sun, D, Spector, TD, Chen, YDI, Damcott, C, Shuldiner, AR, Absher, DM, Horvath, S, Tsao, PS, Kardia, S, Psaty, BM, Sotoodehnia, N, Bell, JT, Ingelsson, E, Chen, W, Dehghan, A, Arnett, DK, Waldenberger, M, Hou, L, Whitsel, EA, Baccarelli, A, Levy, D, Fornage, M, Irvin, MR & Assimes, TL 2021, 'A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids', Nature Communications, vol. 12, no. 1, 3987. https://doi.org/10.1038/s41467-021-23899-y

TY - JOUR

T1 - A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

AU - Jhun, Mina A.

AU - Mendelson, Michael

AU - Wilson, Rory

AU - Gondalia, Rahul

AU - Joehanes, Roby

AU - Salfati, Elias

AU - Zhao, Xiaoping

AU - Braun, Kim Valeska Emilie

AU - Do, Anh Nguyet

AU - Hedman, Åsa K.

AU - Zhang, Tao

AU - Carnero-Montoro, Elena

AU - Shen, Jincheng

AU - Bartz, Traci M.

AU - Brody, Jennifer A.

AU - Montasser, May E.

AU - O’Connell, Jeff R.

AU - Yao, Chen

AU - Xia, Rui

AU - Boerwinkle, Eric

AU - Grove, Megan

AU - Guan, Weihua

AU - Liliane, Pfeiffer

AU - Singmann, Paula

AU - Müller-Nurasyid, Martina

AU - Meitinger, Thomas

AU - Gieger, Christian

AU - Peters, Annette

AU - Zhao, Wei

AU - Ware, Erin B.

AU - Smith, Jennifer A.

AU - Dhana, Klodian

AU - van Meurs, Joyce

AU - Uitterlinden, Andre

AU - Ikram, Mohammad Arfan

AU - Ghanbari, Mohsen

AU - Zhi, Deugi

AU - Gustafsson, Stefan

AU - Lind, Lars

AU - Li, Shengxu

AU - Sun, Dianjianyi

AU - Spector, Tim D.

AU - Chen, Yii der Ida

AU - Damcott, Coleen

AU - Shuldiner, Alan R.

AU - Absher, Devin M.

AU - Horvath, Steve

AU - Tsao, Philip S.

AU - Kardia, Sharon

AU - Psaty, Bruce M.

AU - Sotoodehnia, Nona

AU - Bell, Jordana T.

AU - Ingelsson, Erik

AU - Chen, Wei

AU - Dehghan, Abbas

AU - Arnett, Donna K.

AU - Waldenberger, Melanie

AU - Hou, Lifang

AU - Whitsel, Eric A.

AU - Baccarelli, Andrea

AU - Levy, Daniel

AU - Fornage, Myriam

AU - Irvin, Marguerite R.

AU - Assimes, Themistocles L.

N1 - Funding Information: We thank our Amish community and research volunteers for their long-standing partnership in research, and acknowledge the dedication of our Amish liaisons, field workers and the Amish Research Clinic staff, without which these studies would not have been possible. We thank the staff and participants of the ARIC study for their important contributions. We would also like to thank the families that participated in the GENOA study. The authors are grateful to the Rotterdam Study participants, the staff involved with the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of the Illumina 450 K methylation array data (EWAS data) for the Rotterdam Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We thank Mr. Michael Verbiest, Ms. Mila Jhamai, Ms. Sarah Higgins, Mr. Marijn Verkerk, and Lisette Stolk PhD for their help in creating the methylation database. We thank Ms. Mila Jhamai, Ms. Sarah Higgins, Marjolein Peters, MSc, Mr. Marijn Verkerk and Jeroen van Rooij, MSc for their help in creating the RNA array expression database. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant R01HL105756. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I). Funding was also supported by 5RC2HL102419 and R01NS087541. The CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 75N92021D00006; and NHLBI grants U01HL080295, R01HL087652, R01HL092111, R01HL105756, R01HL103612, R01HL111089, R01HL116747, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA) as well as Laughlin Family, Alpha Phi Foundation, and Locke Charitable Foundation. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Framingham Heart Study is funded by National Institutes of Health contract N01-HC-25195. The laboratory work for this investigation was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health and an NIH Director’s Challenge Award (D. Levy, Principal Investigator). The GOLDN epigenetics study is funded by the NIH National Heart, Lung, and Blood Institute grant R01 HL104135-01. Support for the Genetic Epidemiology Network of Arteriopathy (GENOA) was provided by the National Heart, Lung and Blood Institute (HL054457, HL100185, HL119443, and HL133221) of the National Institutes of Health. German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. This work was supported by a grant (WA 4081/1-1) from the German Research Foundation. The TwinsUK epigenetic study received support from the ESRC (ES/N000404/1). The TwinsUK study funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007–2013); National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. The PIVUS study was supported by Swedish Research Council (Grant no. 2012-1397), Knut och Alice Wallenberg Foundation (Grant no. 2013.0126), Swedish Heart-Lung Foundation (grant no. 20140422), and Swedish Diabetes Foundation (Grant no. 2013-024). The Rotterdam Study EWAS data was funded by the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by the Netherlands Organization for Scientific Research (NWO; project number 184021007) and made available as a Rainbow Project (RP3; BIOS) of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL). The generation and management of RNA-expression array data for the Rotterdam Study was executed and funded by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. The Women’s Health Initiative data, WHI-BA23 and WHI-EMPC, were generated through an NHLBI Broad Agency Announcement contract (HHSN268201300006C) and a National Institute of Environmental Health Sciences grant (R01-ES020836). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Funding Information: Alan R Shuldiner is an employee of Regeneron Pharmaceuticals, Inc. Bruce M Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Kim Valeska Emilie Braun works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc. and AXA. Publisher Copyright: © 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/12

Y1 - 2021/12

N2 - Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.

AB - Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.

UR - http://www.scopus.com/inward/record.url?scp=85108782292&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-23899-y

DO - 10.1038/s41467-021-23899-y

M3 - Article

AN - SCOPUS:85108782292

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3987

ER -

A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

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